慢性乙型肝炎干扰素疗法的适应证选择

目前用于慢性乙型肝炎抗病毒治疗的干扰素主要是ＩＦＮ α，其适应证基本只有一个，即ＨＢＶ复制活跃的活动性慢性乙型肝炎。 慢性乙型肝炎有经典型（ｃｌａｓｓｉｃａｌ）和异型（ａｔｙｐｉｃａｌ）之分。经典型的血清病毒学标志特征是血清Ｈ ＢｓＡ ｇ ＋、ＨＢｅＡｇ＋和抗－ＨＢｃ＋、血清ＨＢＶＤＮＡ十，由野生株ＨＢＶ感染所致，也称ＨＢｅＡｇ阳性慢性乙型肝炎；异型的血清病毒学标志特征是血清ＨＢＳＡｇ＋、抗ＨＢｅ＋和抗ＨＢｃ＋，血清ＨＢＶ ＤＮＡ＋，主要由前Ｃ基因变异株或Ｘ区Ｃ基因启动子变异株ＨＢＶ感染所致，也称抗－…     

乙型肝炎患者免疫促进剂治疗前后T淋巴细胞亚群及NK细胞的…

对６２例慢乙肝患者Ｔ淋巴细胞亚群及ＮＫ细胞检测，并观察分别经ｉＲＮＡ、猪苓多糖及ＬＡＫ细胞治疗前后的细胞数量变化。结果发现治疗前ＣＤ＾＋４细胞降低，ＣＤ＾＋８细胞增高。ＣＤ＾＋４／ＣＤ＾＋８比值下降。治疗后ＣＤ＾＋４细胞及ＮＫ细胞增高，ＣＤ＾＋４／ＣＤ＾＋８比值上升，其中以ＬＡＫ细胞治疗效果显著，与ＨＢＶＭ转阴呈正相关。说明提高机体免疫功能对清除病毒有一定作用。     

CD+4自然杀伤T细胞在慢性乙型肝炎病毒感染中的作用

目的 了解ＣＤ４＾＋、ＣＤ８＾＋自然杀伤（ＮＫ）Ｔ细胞在慢性ＨＢＶ感染外周轿中的分布情况,并对其细胞毒性进行分析,阐明其在慢性ＨＢＶ感染中的作用。方法 常规分离外周上核细胞（ＰＢＭＣＳ）,用重组人白细胞介素－１２／２诱导１４ｄ,以鼠抗人ＣＤ４单克隆抗体或抗人ＣｍＡｂ与抗人ＣＤ５６ｍＡｂ分别标记细胞样品,流式细胞术（ＦＣＭ）分析,ＣＤ４＋ＣＤ５６＾＋同时阳性的细胞,即为ＣＤ４＾＋－ＮＫ－Ｔ细胞;Ｃ     

LAK细胞治疗慢性乙,丙型肝炎疗效及免疫机制研究

报道应用自体ＬＡＫ细胞回输治疗１１０例慢性乙型肝炎（乙肝）和２０例慢性丙型肝炎（丙肝）的结果。疗程结束时慢性乙肝治疗组ＨＢｅＡｇ阴转率、抗－ＨＢｅ阳转率和ＨＢｖＤＮＡ阴转率分别为４６，４％、３５．５％和４８．２％，与对照组相比明显提高（Ｐ均〈０．００５）；２ｏ例慢性丙肝经治疗后抗－ＨＣＶ阴转２例（１０％），ＨＣＶＲＮＡ阴转４例（２０％），而对照组维持不变。进而对ＬＡＫ治疗的免疫机制进行探讨，结果发现ＬＡＫ治疗后ＣＡＨ患者ＣＤ＋４阳性率、ＣＤ＋４／ｃＤ＋８比值均增高（Ｐ＜０．０５），外周血单个核细胞膜白细胞介素－２受体（ｍＩＬ－２Ｒ）和血清中可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）的水平也明显升高（Ｐ＜０．０１）。     

乙型肝炎病毒前核心区基因变异的研究

应用聚合酶链（ＰＣＲ）方法，分别扩增乙型肝炎病毒（ＨＢＶ）标志为ＨＢｓＡｇ（＋），ＨＢｅＡｇ（＋）抗ＨＢｃ（＋）的慢性乙型肝炎（ＣＨＢ）１８例（第一组，ＨＢＶ标志物为ＨＢｓＡｇ（＋），抗ＨＢｅ（＋）和抗ＨＢｃ（＋）的慢性乙型肝炎２１例（第二组，以及ＨＢＶ标志与第二组相同的体检健康的正常人１５例（第三组），其ＰＣＲ的阳性率分别为８３．３％，７１．４％和３３．３％，第二组与第三组要紫有显著差异（Ｐ〈０     

抗HBe(+)慢性乙型肝炎的重组干扰素治疗应答及其影响因素

目的探讨抗ＨＢｅ／ＨＢＶＤＮＡ（＋）慢性乙型肝炎（ＣＨＢ）的干扰素治疗效果及其影响因素。方法对１５例ＨＢｅ（＋）和２５例ＨＢｅＡｇ（＋）ＣＨＢ患者用重组干扰素α－１ｂ治疗，治疗前、后和随访半年后检测ＨＢＶ及前Ｃ区Ａ１８９６终止变异。结果抗ＨＢｅ（＋）慢性乙型肝炎干扰素治疗近期应答率为７３％（１１／１５），与ＨＢｅＡｇ（＋）组比较差异无显著性（Ｐ＞００５）；治疗前抗ＨＢｅ（＋）组ＨＢＶＤＮＡ含量明显低于ＨＢｅＡｇ（＋）组（Ｐ＜０００５）；但前Ｃ区Ａ１８９６变异检出率４７％（７／１５）显著高于ＨＢｅＡｇ（＋）组的１６％（４／２５），Ｐ＜００５；４例复发者都是Ａ１８９６变异感染。结论血清ＨＢＶＤＮＡ水平可能是影响其应答的重要因素，前Ｃ区Ａ１８９６变异并不影响干扰素的近期应答率，但可能是其复发的一个重要因素。     

HDV感染与HBV血清标志物的关系

目的分析ＨＤＶ感染与ＨＢＶ血清标志物的关系方法选ＨＢＶ血清标志物阳性患者，同时进行ＨＤＶ感染的检测．供血员做正常对照．ＨＤＶ感染和ＨＢＶ血清标志物皆用相应酶联免疫吸附实验（ＥＬＩＳＡ）．结果２８９例ＨＢＶ血清标志物阳性患者中，有４０例ＨＤＶ感染阳性，阳性率为１３８％．在ＨＢＳＡｂ（＋）组，无ＨＤＶ感染阳性者检出；在ＨＢＳＡｇ（＋）或ＨＢＣＡｂ（＋）或ＨＢｅＡｂ（＋）组患者中，ＨＤＶ感染阳性率分别达１７６％，１８８％、２５２％，明显高于ＨＢｅＡｇ（＋）组（１０９％）；并且ＨＤＶ感染阳性率在ＨＢＳＡｇ·ＨＢＣＡｂ·ＨＢｅＡｂ（＋）患者中，高达２６２％，明显高于ＨＢＳＡｇ·ＨＢＣＡｂ·ＨＢｅＡｇ（＋）者（１０９％）．结论①ＨＤＶ感染性率在ＨＢＳＡｇ·ＨＢＣＡｂ·ＨＢｅＡｂ（＋）患者中高于ＨＢＳＡｇ·ＨＢＣＡｂ·ＨＢｅＡｇ（＋）患者．②ＨＤＶ感染阳性率与ＨＢＶ复制的速度和数量不全相关．     

乙型肝炎免疫的供者的骨髓用作移植以清除乙型肝炎病毒

乙型肝炎病毒(ＨＢＶ)初期感染可以通过体液和细胞免疫反应使ＨＢＶ得以清除,但ＨＢＶ也可以持续存在,导致慢性乙型肝炎或乙型肝炎表面抗原(ＨＢｓＡｇ)阳性无症状携带状态。应用同种骨髓移植(ＢＭＴ)法使病人ＨＢｓＡｇ得以清除尚无报告。本文报告1例男性,29岁,因患急性髓性白血病于第2次完全缓解期行ＢＭＴ,骨髓供者是与其ＨＬＡ匹配的妹妹。ＢＭＴ前病人系无症状ＨＢＶ携带者(ＨＢｓＡｇ、抗ＨＢｃ和抗ＨＢｅ阳性,抗ＨＢｓ和ＨＢｅＡｇ阴性),巢式ＰＣＲ法检出其正常肝组织中有ＨＢＶＤＮＡ,但血清ＨＢＶＤＮＡ阴性。其妹妹为ＨＢｓＡｇ、…     

慢性乙型肝炎患者HBcAg特异性Th细胞克隆的建立及初步分析

为了解Ｔｈ细胞极化群体在慢性乙型肝炎 (ＣＨＢ)患者外周血及肝组织中的分布情况 ,采用有限稀释法 ,建立了ＣＨＢ患者外周血及肝组织ＨＢｃＡｇ特异性Ｔｈ细胞克隆 ,并对所获得细胞克隆进行分析。发现自肝组织分离的ＨＢｃＡｇ特异性Ｔ细胞克隆 ,92 .5%为ＣＤ4 表型 ,以Ｔｈ1为主 ,而来源于外周血的Ｔ细胞克隆主要以Ｔｈ0为主 ,并与ＨＢｅＡｇ是否阳性无关。仅 15% ( 6/40 )的Ｔ细胞克隆呈现明显的ＨＢｃＡｇ特异性淋巴细胞增殖反应。在肝组织及外周血占主导地位的Ｔｈ细胞极化群的不同 ,较高比例的Ｔｈ1细胞在肝组织炎症局部的聚集 ,提示…     

乙型慢性活动性肝炎患者外周血淋巴细胞亚群白细胞介素一2受体的初探

应用间接免疫荧光法，放射免疫分析法，微量细胞培养法及斑点杂交技术，检测了２７例乙型慢性活动性肝炎（ＣＡＨ一Ｂ）患者及７例正常对照者ＣＤ＋４、ＣＤ＋８及Ｂ细胞膜上白细胞介素一２受体（ｍＩＬ－２Ｒ，ＣＤ２５抗原为其β链），各亚群细胞培养上清及病人同期血清中可溶性白细胞介素一２受体（ｓＩＬ－２Ｒ），ＣＤ＋４细胞培养上清中ＩＬ一２活性。结果：ＣＡＨ－Ｂ病人外周血ＣＤ２５抗原阳性的ＣＤ＋４、ＣＤ＋８细胞及Ｂ细胞较正常对照者减少，且ＣＤ２５抗原阳性的ＣＤ＋４、ＣＤ＋８细胞减少较Ｂ细胞明显；ＣＤ＋细胞培养上清中ＩＬ一２活性较正常人降低，并与病情的轻重、ＣＤ＋４细胞ｍＩＬ一２Ｒ的表达呈正相关；ＣＡＨ－Ｂ病人血清ｓＩＬ－２Ｒ增高，但培养上清ｓＩＬ－２Ｒ与正常对照无显著性差异。结果提示：ＣＡＨ一Ｂ病人外周血ＣＤ＋４、ＣＤ＋８及Ｂ细胞ｍＩＬ－２Ｒ表达均减弱；ＣＡＨ－Ｂ病人体内Ｔ细胞免疫应答功能受损可能较Ｂ细胞受损明显；ＣＡＨ－Ｂ病人体内ＩＬ一２产生水平低下与病情轻重有某种关联；ＣＡＨ一Ｂ患者血清中增高的ｓＩＬ一２Ｒ可能来自肝内浸润的免疫活性细胞ｍＩＬ－２Ｒβ链脱落。     

Hepatitis B Core Antigen Expression in Hepatocytes Reflects Viral Response to Entecavir in Chronic Hepatitis B Patients

Background/Aims

Hepatitis B core antigen is known to be a major target for virus-specific T cells and also reflects the progression of liver dissease and viral replication. Hepatitis B core antigen expression in hepatocytes leads to altered histological activity, viral replication, and immune response. The purpose of this study is to evaluate whether the topographical distribution of hepatitis B core antigen expression can predict the viral response to entecavir in patients with chronic hepatitis B.

Methods

We enrolled 91 patients with treatment-naïve chronic hepatitis B. All the patients underwent liver biopsy, and the existence and pattern of hepatitis B core antigen evaluated by immunohistochemistry. All patients received 0.5 mg of entecavir daily following a liver biopsy. We checked the viral response at 3, 6, and 12 months during antiviral therapy.

Results

Of the 91 patients, 64 (70.3%) had hepatitis B core antigen expression. Of the subcellular patterns, the mixed type was dominant (n=48, 75%). The viral response was significantly higher in the hepatitis B core antigen-negative group than in the hepatitis B core antigen-positive group (88.9% and 54.7%, respectively; p=0.001) after 12 months of entecavir therapy.

Conclusions

Chronic hepatitis B patients who are hepatitis B core antigen-negative have a better response to entecavir therapy than do hepatitis B core antigen-positive patients.     

Hepatitis B Splice-Generated Protein Antibodies in Syrian Chronic Hepatitis B Patients: Incidence and Significance

Background:

Previous studies have suggested hepatitis B splice-generated protein (HBSP), when expressed, is involved in the pathogenesis of HBV infection.

Objectives:

We aimed to evaluate anti-HBSP incidence and association with several HBV infection parameters in a group of Syrian chronic hepatitis B patients.

Patients and Methods:

Eighty treatment-naïve HBsAg-positive adult chronic hepatitis B patients'' sera were included in our prospective targeted study. Liver function, virological and histological tests results were obtained from patients’ medical files. Three variants of a 20-mer HBSP-derived peptide were designed based on HBV genome sequences obtained from Syrian patients'' sera (GenBank Accession No. {"type":"entrez-nucleotide-range","attrs":{"text":"JN257148-JN257217","start_term":"JN257148","end_term":"JN257217","start_term_id":"364505024","end_term_id":"364505559"}}JN257148-JN257217). Microtiter plate wells were coated with the synthetic peptides and used to detect anti-HBSP antibodies by an optimized indirect enzyme-linked immunosorbent assay (ELISA). Samples were considered positive when showed optical density (OD) values higher than the cut-off value for at least one peptide variant.

Results:

Seven out of eighty (9%) CHB patients were positive for anti-HBSP antibodies. Mean OD values were not significantly different between HBeAg-positive and -negative patients (P > 0.05). OD values showed weak positive correlation with ALT and AST values (P < 0.05), and weak to moderate positive correlation with liver biopsy staging ranks (P < 0.05). No significant correlation was revealed with viral load values or liver biopsy grading ranks (P > 0.05).

Conclusions:

We introduced an anti-HBSP antibodies ELISA, designed for locally circulating HBV strains. Correlation observed of Anti-HBSP with liver fibrosis staging regardless of viral replication and liver inflammation suggests anti-HBSP antibodies as possible indicator for HBV-associated liver fibrosis.     

黄腐酸钠与抗—HBI RNA联合治疗慢性乙型肝炎疗效观察

目的:观察联合用药治疗慢性乙型肝炎的疗效。方法:将HRsAg、HBeAg\HBV-DNA均为阳性,谷丙转氨酶(ALT)间断或反复增高的70例慢性乙肝病人,随机分成两组门诊治疗。治疗组采用黄腐酸钠(Sodium Fuliate,简称SF),与肌注抗乙肝免疫核糖核酸2mg/qod治疗;对照组仅肌注抗乙肝免疫核糖核酸2mg/qod,均连续用3个月。治疗结束时及结束后3个月复查乙肝病毒指标及ALT。结果:治疗组与对照组HBeAg、HBV-DNA阴转率分别为52.5％、47.5％及26.6％、23.4％(P<0.05)。SF与抗乙肝免疫核糖核酸联合组治疗慢性乙肝,近期疗效优于单用抗乙肝免疫核糖核酸组。结论:黄腐酸钠与抗HBI RNA联合用药可进一步调节患者免疫功能,抑制HBV复制,提高细胞生物活性等。     

Combination Therapy in Liver Transplant Recipients with Hepatitis B Virus Without Hepatitis B Immune Globulin

Introduction: Conventional therapy to prevent HBV recurrence in liver transplant (LTx) recipients consists of Hepatitis B Immune Globulin (HBIg). The aim of this review is to investigate the safety and efficacy of converting HBIg and LAM therapy to ADV and LAM therapy. Methods: A retrospective review involving all liver transplant patients with HBV maintained on HBIg and LAM therapy. Results collected included: gender, age, HBV serological and DNA status (COBAS AmpliScreen PCR-based testing). Serologic testing was done every three months. Patients were followed for drug reactions, therapy compliance, and immune suppression compliance. A cost benefit analysis was done for drug comparisons using United States currency values. Results: Patient demographics included: Male (n=6), Female (n=4), mean age 44 years (range 33 to 65). The mean length of follow up since therapy conversion (from HBIg and LMV to ADV and LMV) was 21 months (range 16 to 25 months). Serological status at time of conversion revealed that DNA status remained negative in all patients, HBsAg negative in 10/10, HB eAg (+) (5/10) and HBeAb (+)(5/10). None of the patients experienced an increase in transaminases while on dual ADV and LAM therapy. All patients were maintained on immune suppression monotherapy (tacrolimus) at 7–9 ng/mL. All patients reported compliance with the dual therapy and that they experienced no drug related side effects. Mean yearly costs for ADV and LAM was 7,235.00 United States dollars (range 6,550.00 to 8,225.00); while mean monthly costs for HBIg and LAM; 9225.00 (range 7205.00 to 12005.00). Conclusion: The above results demonstrate beneficial effects of ADV and LAM in place of the current standard of HBIg and LAM therapy. Safety and short term results show nucleoside therapy is adequate at preventing HBV viral recurrence. Lastly, the economic benefit for ADV and LAM vastly outweighed the HBIg and LAM group.